MCID: 3MT022
MIFTS: 27

3-Methylglutaconic Aciduria with Cataracts, Neurologic Involvement, and Neutropenia

Categories: Genetic diseases, Neuronal diseases, Eye diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for 3-Methylglutaconic Aciduria with Cataracts, Neurologic...

MalaCards integrated aliases for 3-Methylglutaconic Aciduria with Cataracts, Neurologic Involvement, and Neutropenia:

Name: 3-Methylglutaconic Aciduria with Cataracts, Neurologic Involvement, and Neutropenia 57 29 6
3-Methylglutaconic Aciduria, Type Vii, with Cataracts, Neurologic Involvement and Neutropenia 57 75 40
3-Methylglutaconic Aciduria with Cataracts, Neurologic Involvement and Neutropenia 12 75 15
Megcann 57 12 75
Mgca7 57 12 75
3-Methylglutaconic Aciduria, Type Vii 57 75
3-Methylglutaconic Aciduria Type 7 12 59
Mga7 12 59
3-Methylglutaconic Aciduria-Cataract-Neurologic Involvement-Neutropenia Syndrome 59
3-Methylglutaconic Aciduria, Type Vii; Mgca7 57
3-Methylglutaconic Aciduria Type Vii 12
3-Methylglutaconic Aciduria 7 75

Characteristics:

Orphanet epidemiological data:

59
3-methylglutaconic aciduria type 7
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal; Age of death: early childhood,infantile;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
highly variable phenotype
onset at birth
onset in utero in severely affected patients
death often in childhood


HPO:

32
3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia:
Onset and clinical course congenital onset phenotypic variability progressive
Inheritance autosomal recessive inheritance


Classifications:



Summaries for 3-Methylglutaconic Aciduria with Cataracts, Neurologic...

OMIM : 57 3-Methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia (MEGCANN) is an autosomal recessive inborn error of metabolism characterized primarily by increased levels of 3-methylglutaconic acid (3-MGA) associated with neurologic deterioration and neutropenia. The phenotype is highly variable: most patients have infantile onset of a progressive encephalopathy with various movement abnormalities and delayed psychomotor development, although rare patients with normal neurologic development have been reported. Other common, but variable, features include cataracts, seizures, and recurrent infections (summary by Wortmann et al., 2015 and Saunders et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA1 (250950). (616271)

MalaCards based summary : 3-Methylglutaconic Aciduria with Cataracts, Neurologic Involvement, and Neutropenia, also known as 3-methylglutaconic aciduria, type vii, with cataracts, neurologic involvement and neutropenia, is related to clpb deficiency and 3-methylglutaconic aciduria, type viii. An important gene associated with 3-Methylglutaconic Aciduria with Cataracts, Neurologic Involvement, and Neutropenia is CLPB (ClpB Homolog, Mitochondrial AAA ATPase Chaperonin). Affiliated tissues include bone, eye and bone marrow, and related phenotypes are intellectual disability and seizures

Disease Ontology : 12 A 3-methylglutaconic aciduria that has material basis in homozygous or compound heterozygous mutation in the CLPB gene on chromosome 11q13.

UniProtKB/Swiss-Prot : 75 3-methylglutaconic aciduria with cataracts, neurologic involvement and neutropenia: An autosomal recessive inborn error of metabolism with a highly variable phenotype. Primary disease symptoms are increased levels of 3-methylglutaconic acid, neurologic deterioration and neutropenia. Other common features include progressive encephalopathy, movement abnormalities, delayed psychomotor development, cataracts, seizures, and recurrent infections.

Related Diseases for 3-Methylglutaconic Aciduria with Cataracts, Neurologic...

Diseases related to 3-Methylglutaconic Aciduria with Cataracts, Neurologic Involvement, and Neutropenia via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 clpb deficiency 11.5
2 3-methylglutaconic aciduria, type viii 11.3

Symptoms & Phenotypes for 3-Methylglutaconic Aciduria with Cataracts, Neurologic...

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
intellectual disability
spasticity
cerebellar atrophy
cerebral atrophy
extrapyramidal signs
more
Abdomen Gastrointestinal:
poor feeding

Muscle Soft Tissue:
hypotonia, neonatal
increased muscle tone, neonatal (in severely affected patients)

Head And Neck Face:
dysmorphic facial features (in some patients)

Laboratory Abnormalities:
increased urinary 2-methylglutaconic acid

Head And Neck Head:
microcephaly

Immunology:
recurrent infections (in some patients)
neutropenia (in most patients)
bone marrow shows deficient granulopoiesis

Growth Other:
poor growth

Head And Neck Eyes:
cataracts (in most patients)


Clinical features from OMIM:

616271

Human phenotypes related to 3-Methylglutaconic Aciduria with Cataracts, Neurologic Involvement, and Neutropenia:

32 (show all 17)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 32 HP:0001249
2 seizures 32 occasional (7.5%) HP:0001250
3 spasticity 32 HP:0001257
4 developmental regression 32 occasional (7.5%) HP:0002376
5 abnormal pyramidal signs 32 HP:0007256
6 cataract 32 hallmark (90%) HP:0000518
7 global developmental delay 32 hallmark (90%) HP:0001263
8 abnormal facial shape 32 occasional (7.5%) HP:0001999
9 microcephaly 32 HP:0000252
10 neonatal hypotonia 32 HP:0001319
11 feeding difficulties 32 HP:0011968
12 growth delay 32 HP:0001510
13 recurrent infections 32 occasional (7.5%) HP:0002719
14 neutropenia 32 hallmark (90%) HP:0001875
15 abnormality of extrapyramidal motor function 32 HP:0002071
16 cerebellar atrophy 32 HP:0001272
17 cerebral atrophy 32 HP:0002059

Drugs & Therapeutics for 3-Methylglutaconic Aciduria with Cataracts, Neurologic...

Search Clinical Trials , NIH Clinical Center for 3-Methylglutaconic Aciduria with Cataracts, Neurologic Involvement, and Neutropenia

Genetic Tests for 3-Methylglutaconic Aciduria with Cataracts, Neurologic...

Genetic tests related to 3-Methylglutaconic Aciduria with Cataracts, Neurologic Involvement, and Neutropenia:

# Genetic test Affiliating Genes
1 3-Methylglutaconic Aciduria with Cataracts, Neurologic Involvement, and Neutropenia 29 CLPB

Anatomical Context for 3-Methylglutaconic Aciduria with Cataracts, Neurologic...

MalaCards organs/tissues related to 3-Methylglutaconic Aciduria with Cataracts, Neurologic Involvement, and Neutropenia:

41
Bone, Eye, Bone Marrow

Publications for 3-Methylglutaconic Aciduria with Cataracts, Neurologic...

Variations for 3-Methylglutaconic Aciduria with Cataracts, Neurologic...

UniProtKB/Swiss-Prot genetic disease variations for 3-Methylglutaconic Aciduria with Cataracts, Neurologic Involvement, and Neutropenia:

75 (show all 11)
# Symbol AA change Variation ID SNP ID
1 CLPB p.Thr268Met VAR_073397 rs200032855
2 CLPB p.Tyr272Cys VAR_073398 rs777313457
3 CLPB p.Arg408Gly VAR_073399 rs144078282
4 CLPB p.Met411Ile VAR_073400 rs786205137
5 CLPB p.Cys486Arg VAR_073402 rs886041118
6 CLPB p.Glu501Lys VAR_073403 rs748915609
7 CLPB p.Tyr567Cys VAR_073404 rs150857620
8 CLPB p.Ala591Val VAR_073405 rs748010262
9 CLPB p.Tyr617Cys VAR_073406 rs786205138
10 CLPB p.Gly646Val VAR_073407 rs759500860
11 CLPB p.Ile682Asn VAR_073408 rs886041120

ClinVar genetic disease variations for 3-Methylglutaconic Aciduria with Cataracts, Neurologic Involvement, and Neutropenia:

6
(show top 50) (show all 80)
# Gene Variation Type Significance SNP ID Assembly Location
1 CLPB NM_030813.5(CLPB): c.1305_1307invGGG (p.Glu435_Gly436delinsAsp) inversion Pathogenic GRCh38 Chromosome 11, 72301915: 72301917
2 CLPB NM_030813.5(CLPB): c.1305_1307invGGG (p.Glu435_Gly436delinsAsp) inversion Pathogenic GRCh37 Chromosome 11, 72012959: 72012961
3 CLPB NM_030813.5(CLPB): c.1937G> T (p.Gly646Val) single nucleotide variant Pathogenic rs759500860 GRCh38 Chromosome 11, 72293554: 72293554
4 CLPB NM_030813.5(CLPB): c.1937G> T (p.Gly646Val) single nucleotide variant Pathogenic rs759500860 GRCh37 Chromosome 11, 72004598: 72004598
5 CLPB NM_030813.5(CLPB): c.1772C> T (p.Ala591Val) single nucleotide variant Pathogenic rs748010262 GRCh38 Chromosome 11, 72294125: 72294125
6 CLPB NM_030813.5(CLPB): c.1772C> T (p.Ala591Val) single nucleotide variant Pathogenic rs748010262 GRCh37 Chromosome 11, 72005169: 72005169
7 CLPB NM_030813.5(CLPB): c.1233G> A (p.Met411Ile) single nucleotide variant Pathogenic rs786205137 GRCh38 Chromosome 11, 72302328: 72302328
8 CLPB NM_030813.5(CLPB): c.1233G> A (p.Met411Ile) single nucleotide variant Pathogenic rs786205137 GRCh37 Chromosome 11, 72013372: 72013372
9 CLPB NM_030813.5(CLPB): c.1850A> G (p.Tyr617Cys) single nucleotide variant Pathogenic rs786205138 GRCh37 Chromosome 11, 72005091: 72005091
10 CLPB NM_030813.5(CLPB): c.1850A> G (p.Tyr617Cys) single nucleotide variant Pathogenic rs786205138 GRCh38 Chromosome 11, 72294047: 72294047
11 CLPB NM_030813.5(CLPB): c.1222A> G (p.Arg408Gly) single nucleotide variant Pathogenic/Likely pathogenic rs144078282 GRCh38 Chromosome 11, 72302339: 72302339
12 CLPB NM_030813.5(CLPB): c.1222A> G (p.Arg408Gly) single nucleotide variant Pathogenic/Likely pathogenic rs144078282 GRCh37 Chromosome 11, 72013383: 72013383
13 CLPB NM_030813.5(CLPB): c.1249C> T (p.Arg417Ter) single nucleotide variant Pathogenic rs200203460 GRCh38 Chromosome 11, 72302312: 72302312
14 CLPB NM_030813.5(CLPB): c.1249C> T (p.Arg417Ter) single nucleotide variant Pathogenic rs200203460 GRCh37 Chromosome 11, 72013356: 72013356
15 CLPB NM_030813.5(CLPB): c.803C> T (p.Thr268Met) single nucleotide variant Uncertain significance rs200032855 GRCh37 Chromosome 11, 72069986: 72069986
16 CLPB NM_030813.5(CLPB): c.803C> T (p.Thr268Met) single nucleotide variant Uncertain significance rs200032855 GRCh38 Chromosome 11, 72358942: 72358942
17 CLPB NM_030813.5(CLPB): c.961A> T (p.Lys321Ter) single nucleotide variant Pathogenic rs786205139 GRCh38 Chromosome 11, 72329709: 72329709
18 CLPB NM_030813.5(CLPB): c.961A> T (p.Lys321Ter) single nucleotide variant Pathogenic rs786205139 GRCh37 Chromosome 11, 72040753: 72040753
19 CLPB NM_030813.5(CLPB): c.1685delT (p.Ile562Thrfs) deletion Pathogenic rs876657402 GRCh37 Chromosome 11, 72005454: 72005454
20 CLPB NM_030813.5(CLPB): c.1685delT (p.Ile562Thrfs) deletion Pathogenic rs876657402 GRCh38 Chromosome 11, 72294410: 72294410
21 CLPB NM_030813.5(CLPB): c.668G> A (p.Ser223Asn) single nucleotide variant Likely benign rs143097446 GRCh37 Chromosome 11, 72084037: 72084037
22 CLPB NM_030813.5(CLPB): c.668G> A (p.Ser223Asn) single nucleotide variant Likely benign rs143097446 GRCh38 Chromosome 11, 72372993: 72372993
23 CLPB NM_030813.5(CLPB): c.2045T> A (p.Ile682Asn) single nucleotide variant Pathogenic rs886041120 GRCh38 Chromosome 11, 72293446: 72293446
24 CLPB NM_030813.5(CLPB): c.2045T> A (p.Ile682Asn) single nucleotide variant Pathogenic rs886041120 GRCh37 Chromosome 11, 72004490: 72004490
25 CLPB NM_030813.5(CLPB): c.1937dupG (p.Cys647Leufs) duplication Pathogenic rs886041119 GRCh38 Chromosome 11, 72293554: 72293554
26 CLPB NM_030813.5(CLPB): c.1937dupG (p.Cys647Leufs) duplication Pathogenic rs886041119 GRCh37 Chromosome 11, 72004598: 72004598
27 CLPB NM_030813.5(CLPB): c.1915G> A (p.Glu639Lys) single nucleotide variant Pathogenic rs375934856 GRCh38 Chromosome 11, 72293576: 72293576
28 CLPB NM_030813.5(CLPB): c.1915G> A (p.Glu639Lys) single nucleotide variant Pathogenic rs375934856 GRCh37 Chromosome 11, 72004620: 72004620
29 CLPB NM_030813.5(CLPB): c.1882C> T (p.Arg628Cys) single nucleotide variant Uncertain significance rs150343959 GRCh37 Chromosome 11, 72004653: 72004653
30 CLPB NM_030813.5(CLPB): c.1882C> T (p.Arg628Cys) single nucleotide variant Uncertain significance rs150343959 GRCh38 Chromosome 11, 72293609: 72293609
31 CLPB NM_030813.5(CLPB): c.1700A> G (p.Tyr567Cys) single nucleotide variant Pathogenic rs150857620 GRCh38 Chromosome 11, 72294395: 72294395
32 CLPB NM_030813.5(CLPB): c.1700A> G (p.Tyr567Cys) single nucleotide variant Pathogenic rs150857620 GRCh37 Chromosome 11, 72005439: 72005439
33 CLPB NM_030813.5(CLPB): c.1501G> A (p.Glu501Lys) single nucleotide variant Pathogenic rs748915609 GRCh38 Chromosome 11, 72295567: 72295567
34 CLPB NM_030813.5(CLPB): c.1501G> A (p.Glu501Lys) single nucleotide variant Pathogenic rs748915609 GRCh37 Chromosome 11, 72006611: 72006611
35 CLPB NM_030813.5(CLPB): c.1456T> C (p.Cys486Arg) single nucleotide variant Pathogenic rs886041118 GRCh38 Chromosome 11, 72295612: 72295612
36 CLPB NM_030813.5(CLPB): c.1456T> C (p.Cys486Arg) single nucleotide variant Pathogenic rs886041118 GRCh37 Chromosome 11, 72006656: 72006656
37 CLPB NM_030813.5(CLPB): c.815A> G (p.Tyr272Cys) single nucleotide variant Pathogenic rs777313457 GRCh38 Chromosome 11, 72358930: 72358930
38 CLPB NM_030813.5(CLPB): c.815A> G (p.Tyr272Cys) single nucleotide variant Pathogenic rs777313457 GRCh37 Chromosome 11, 72069974: 72069974
39 CLPB NM_030813.5(CLPB): c.805G> A (p.Ala269Thr) single nucleotide variant Pathogenic rs886041117 GRCh37 Chromosome 11, 72069984: 72069984
40 CLPB NM_030813.5(CLPB): c.805G> A (p.Ala269Thr) single nucleotide variant Pathogenic rs886041117 GRCh38 Chromosome 11, 72358940: 72358940
41 CLPB NM_030813.5(CLPB): c.748C> T (p.Arg250Ter) single nucleotide variant Pathogenic rs777202372 GRCh38 Chromosome 11, 72358997: 72358997
42 CLPB NM_030813.5(CLPB): c.748C> T (p.Arg250Ter) single nucleotide variant Pathogenic rs777202372 GRCh37 Chromosome 11, 72070041: 72070041
43 CLPB NM_030813.5(CLPB): c.1519C> T (p.Leu507=) single nucleotide variant Benign/Likely benign rs77345581 GRCh37 Chromosome 11, 72006593: 72006593
44 CLPB NM_030813.5(CLPB): c.1519C> T (p.Leu507=) single nucleotide variant Benign/Likely benign rs77345581 GRCh38 Chromosome 11, 72295549: 72295549
45 CLPB NM_030813.5(CLPB): c.884G> C (p.Arg295Thr) single nucleotide variant Benign rs7938203 GRCh37 Chromosome 11, 72040830: 72040830
46 CLPB NM_030813.5(CLPB): c.884G> C (p.Arg295Thr) single nucleotide variant Benign rs7938203 GRCh38 Chromosome 11, 72329786: 72329786
47 CLPB NM_030813.5(CLPB): c.866-10C> G single nucleotide variant Benign/Likely benign rs141271919 GRCh37 Chromosome 11, 72040858: 72040858
48 CLPB NM_030813.5(CLPB): c.866-10C> G single nucleotide variant Benign/Likely benign rs141271919 GRCh38 Chromosome 11, 72329814: 72329814
49 CLPB NM_030813.5(CLPB): c.1950C> T (p.Arg650=) single nucleotide variant Benign rs35401939 GRCh37 Chromosome 11, 72004585: 72004585
50 CLPB NM_030813.5(CLPB): c.1950C> T (p.Arg650=) single nucleotide variant Benign rs35401939 GRCh38 Chromosome 11, 72293541: 72293541

Expression for 3-Methylglutaconic Aciduria with Cataracts, Neurologic...

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Pathways for 3-Methylglutaconic Aciduria with Cataracts, Neurologic...

GO Terms for 3-Methylglutaconic Aciduria with Cataracts, Neurologic...

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